A dual genetic tracing system identifies diverse and dynamic origins of cardiac valve mesenchyme
Abstract
In vivo genomic engineering is instrumental for studying developmental biology and regenerative medicine. Development of novel systems with more site-specific recombinases (SSRs) that complement with the commonly used Cre-loxP would be valuable for more precise lineage tracing and genome editing. Here, we introduce a new SSR system via Nigri-nox. By generating tissue-specific Nigri knock-in and its responding nox reporter mice, we show that the Nigri-nox system works efficiently in vivo by targeting specific tissues. As a new orthogonal system to Cre-loxP, Nigri-nox provides an additional control of genetic manipulation. We also demonstrate how the two orthogonal systems Nigri-nox and Cre-loxP could be used simultaneously to map the cell fate of two distinct developmental origins of cardiac valve mesenchyme in the mouse heart, providing dynamics of cellular contribution from different origins for cardiac valve mesenchyme during development. This work provides a proof-of-principle application of the Nigri-nox system for in vivo mouse genomic engineering. Coupled with other SSR systems, Nigri-nox would be valuable for more precise delineation of origins and cell fates during development, diseases and regeneration.
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At E12.5, EpiMT is initiated in epicardial cells lining the outside of the AVC.
“At E12.5, EpiMT is initiated in epicardial cells lining the outside of the AVC5,59.”
From Cell diversity and plasticity during atrioventricular heart valve EMTs (2023) · cites this paper as [59]
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References 48 · Cited by 51
- Authors
- Liu, K., Yu, W., Tang, M., Tang, J., Liu, X., Liu, Q., Li, Y., He, L., Zhang, L., Evans, S. M., Tian, X., Lui, K. O., & Zhou, B.
- Affiliations
- Chinese Academy of Sciences (CN)
- East China Normal University (CN)
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego 5 , La Jolla, CA 92093 , USA
- Jinan University (CN)
- Chinese University of Hong Kong (HK)
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2018-09-15
- Volume
- 145
- Issue
- 18
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2885556130
- Cited by
- 51
- References
- 48
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 13 · 2022: 6 · 2021: 10 · 2020: 7 · 2019: 6
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Key Research and Development Program of China (2016YFC1300600, 2017YFC1001303, 2018YFA0107900, 2018YFA0108100)
- Chinese Academy of Sciences (XDB19000000, XDA16020204, QYZDB-SSW-SMC003, 2015218, 2060299)
- National Science Foundation of China (31730112, 91639302, 31625019, 81761138040, 31571503, 31501172, 31601168, 31701292, 91749122, 81872241, 81872132, 31801215)
- Shanghai Science and Technology Commission (17ZR1449600, 17ZR1449800)
- Shanghai Yangfan Project (16YF1413400, 18YF1427600)
- Shanghai Rising-Star Program (15QA1404300)
- China Postdoctoral Science Foundation (2016|M600337, 2017|M611634, 2017|M621552, 2016|H0042)
- China Postdoctoral Innovative Talent Support Program (BX201700267)
- China Young Talents Lift Engineering (YESS20160050, 2017QNRC001)
- AstraZeneca
- Research Beyond Borders at Boehringer Ingelheim
- Sanofi
- Royal Society-Newton Advanced Fellowship (NA170109)
- Research Council of Hong Kong (04110515, 14111916, C4024-16W)
- Health and Medical Research Fund (03140346, 04152566)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- site-specific recombinases, Cre-loxP system, lineage tracing, heart development, cell fate mapping
- MeSH terms
- Cadherin 5, Animals, DNA Nucleotidyltransferases, Genetic Engineering, Heart Valves, Mesoderm, Mice, Inbred C57BL, Antigens, CD, Cadherins, Endothelial Cells, Mice, Gene Knock-In Techniques, CRISPR-Cas Systems
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